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Biomedical subjects

J T Smith

Publications and source records attributed to J T Smith.

At least 19 recordsLinked to original sources
PubMed1996

Mobility of Chernobyl-derived 137Cs in a peatbog system within the catchment of the Pripyat River, Belarus.

The behaviour of Chernobyl-derived 137Cs in a hydrologically isolated bog system in the catchment of the Pripyat River, Belarus was investigated. Measurements were made of 137Cs activities in the solids and pore waters of the bog soils, as well as the variability in activity in water draining from the bog. It was found that the radiocaesium activity of the pore water, and hence the measured distribution coefficient, Kd, was dependent upon the pressure at which the water was removed from the soil. Measured values of Kd were of the order 10(2) l/kg at an extraction pressure of 0.8 MPa, approximately one order of magnitude lower than those measured in a similar system, Devoke Water, in the UK [1]. Results of comparative measurements suggested that this was a result of the different pore water extraction techniques used. The vertical migration of radiocaesium was modelled using a solution of the advection-diffusion equation. Using a mass balance approach, it was estimated that 137Cs was removed from the system at a rate of 0.3% of the catchment inventory per year, approximately 8 years after the Chernobyl accident. It was shown that both vertical migration and removal of 137Cs is best modelled using a Kd based on a measurement of pore water held at low pressure in the soil, approximately 10(3) l/kg. 137Cs activities in soil pore waters and in drainage waters were very strongly related to the aqueous potassium concentration, and both showed concentration minima in drainage water during the spring. It was shown that runoff coefficients of radiocaesium from peat bogs 8 years after the Chernobyl accident were approximately one order of magnitude greater than those from unsaturated soils of higher mineral content.

Cesium Radioisotopes↗
PubMed1996

Benign soft-tissue lesions in children.

This article is a review of the common benign soft-tissue lesions of the spine and extremities. Reviewed are the pathophysiology, natural history, appropriate work-up, and treatment options. A recommendation is given to consider the diagnosis as possible malignancy and approach such lesions with caution.

Blood Vessels↗
PubMed1996

Influence of temperature on mutational resistance to 4-quinolones.

Minimum inhibitory concentration (MIC) values of ciprofloxacin (CAS 85721-33-1), ofloxacin (CAS 82419-36-1) or levofloxacin (CAS 100986-85-4) against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis were determined at 37, 30 and 25 degrees C on nutrient agar. With E. coli and S. aureus, reducing the incubation temperature from 37 to 30 to 25 degrees C decreased the MIC values for each drug. With P. aeruginosa, temperature reduction also decreased the MIC values for ciprofloxacin but increased the MICs for ofloxacin or levofloxacin. With S. epidermidis, temperature reduction increased the MICs for ciprofloxacin and ofloxacin but with levofloxacin the MICs were identical at 37 or 25 degrees C but higher at 30 degrees C. Mutants of these bacterial species were selected on nutrient agar containing five times their respective MICs of the 4-quinolones at 37, 30 and 25 degrees C. with S. epidermidis, temperature reduction always reduced its mutation frequency to resist 4-quinolones, whereas with the other three species the effect of temperature was more variable, and in some instances even elevated their mutation rates.

4-Quinolones↗
PubMed1995

Rapid determination of logarithmic partition coefficients between n-octanol and water using micellar electrokinetic capillary chromatography.

Micellar electrokinetic capillary chromatography (MECC) was evaluated as a rapid screening tool for the determination of logarithmic partition coefficients between n-octanol-water (log P(OW)). The technique is performed by electrochromatographing a mixture of standards of known log P(OW). The logarithmic capacity factor of each standard was plotted against its log P(OW) to form a linear calibration curve for a given set of chromatographic conditions. The log P(OW) of an unknown is calculated by using its chromatographically determined capacity factor and extracting the log P(OW) value from the calibration curve. The method was evaluated with a set of model compounds with known log P(OW). The accuracy of the method was examined and found to be within the limits required for screening purposes. The correlation of log P(OW) values determined using HPLC and MECC for some novel compounds was examined. This technique allows the screening of log P(OW) at a rate of four samples per hour with minimal sample requirements (< microgram) and with extremely small solvent waste generated.

1-Octanol↗
PubMed1995

Bactericidal activity of the new 4-quinolones DU-6859a and DV-7751a.

The bactericidal activity of two new 4-quinolones, DU-6859a and DV-7751a, was investigated against strains of Escherichia coli, Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae and Enterococcus faecalis. DU-6859a and DV-7751a were more bactericidal than any 4-quinolone tested previously. Furthermore, DU-6859a was unique among 4-quinolones in being able to kill Ent. faecalis after incubation for only 3 h in nutrient broth. The bactericidal mechanisms of DV-7551a were similar to those of other 4-quinolones, but, uniquely, DU-6859a possessed additional bactericidal mechanisms against both Str. pneumoniae and Ent. faecalis. This may explain the unusually potent bactericidal activity of this agent against these species. These results show that DU-6859a is a unique extended-spectrum 4-quinolone, which should prove to be superior to established 4-quinolones.

Anti-Infective Agents↗
PubMed1995

Validity of newborn oscillometric blood pressure.

The objective of this study was to determine the validity of oscillometric blood pressure in relation to arterial blood pressure. Thirty-one newborns were studied. Clinical characteristics, complications, and treatment interventions were documented. Arterial pressure (every 2 sec) and oscillometric pressure (every 3 min) were concurrently recorded for 1-2 h. Serial observations of oscillometric pressure followed the trend of arterial pressure in the individual newborn. However, the study averaged oscillometric pressures were lower than the arterial pressures: systolic, by 1 mmHg; mean, by 5.3 mmHg (p < 0.0001); and diastolic, by 4.6 mmHg (p < 0.0001). The variance of individual, 15-min averaged, and 1-h averaged observations of oscillometric pressure in relation to arterial pressure was examined. Variance for individual observations may be large. The least variance of oscillometric pressure was in the 1-h averaged mean pressure, in which the difference was +/- 2 mmHg in 77% and +/- 4 mmHg in 95% of observations. Clinical characteristics, with the exception of birth weight and treatment interventions, did not affect the variance of oscillometric pressure. This study implies that the offset in relation to arterial pressure should be established for each oscillometric pressure monitoring system. Hourly averaged mean oscillometric pressure is satisfactory for many newborn assessments and management circumstances. However, arterial pressure may be necessary to accurately document transient hypertension or hypotension or an unstable blood pressure.

Birth Weight↗
PubMed1994

Micellar electrokinetic capillary chromatography with in situ charged micelles: 3. Evaluation of alkylglucoside surfactants as anionic butylboronate complexes.

This article represents an extension to a new approach introduced very recently by our laboratory for the control of the surface charge density as well as the hydrophobic character of micellar phases used in micellar electrokinetic capillary chromatography (MECC). The approach is based on the complexation of polyolic surfactants, e.g., alkylglucosides, with butylboronate to form in situ branched, anionic surfactants. The butylboronate can also incorporate into the micelle via its alkyl tail and acts as a "class I" organic additive that mainly modifies the micelle by decreasing the critical micellar concentration, i.e., increasing the hydrophobic character of the micelle, while exhibiting little influence on the aqueous phase. The net result is an in situ charged micellar entity whose hydrophobic character is dynamically altered. The alkylglucoside-butylboronate micellar phases yielded high separation efficiencies and proved useful in the separation of charged and neutral herbicides as well as the chiral separations of medicarpins and precursors, and dansylated D and L-amino acids in the presence of native or modified cyclodextrin chiral selectors.

Amino Acids↗
PubMed1994

Comparative pharmacokinetics of bismuth from ranitidine bismuth citrate (GR122311X), a novel anti-ulcerant and tripotassium dicitrato bismuthate (TDB).

GR122311X (ranitidine bismuth citrate, Glaxo Group Research Ltd.) is a salt of ranitidine with a complex of bismuth and citric acid which is being developed for the treatment of peptic ulceration. In this study, 4 groups of 12 healthy male subjects were dosed for 10 days with either GR122311X 500 mg bid (301 mg bismuth per day), GR122311X 1.0 g bid (602 mg bismuth per day), tripotassium dicitrato bismuthate (TDB, DeNoltab, Gist Brocades Ltd., Weybridge, England) 240 mg bid (431 mg bismuth per day) or placebo. After the last dose the geometric mean for Cmax for 500 mg bid of GR122311X was 5 ng.g-1, for 1.0 g bid GR122311X it was 12 ng.g-1 and it was 21 ng.g-1 for 240 mg TDB bid. The corresponding trough plasma levels were 2 ng.g-1, 4 ng.g-1 and 4 ng.g-1, respectively. The AUC over a dosing interval after the last dose (AUC tau) were 34 ng.h.g-1, 71 ng.h.g-1 and 79 ng.h.g-1, respectively. The bismuth urinary recoveries over the last dosing interval (Ae tau) were 97 micrograms, 227 micrograms and 309 micrograms, respectively, which is less than 1% of the administered doses. The renal clearance of bismuth was less than the glomerular filtration rate. After adjustment for bismuth dose, the Cmax for GR122311X 500 mg was 35% that of TDB, while for GR122311X 1.0 g the Cmax was 42% that of TDB. Similar differences were observed for Ae tau. In conclusion bismuth pharmacokinetics after oral administration of GR1223311X exhibited lower Ae tau and Cmax, with a much narrower Cmax range than those observed for TDB.

Adolescent↗
PubMed1994

Ranitidine bismuth citrate and ranitidine do not affect gastric emptying of a radio-labelled liquid meal.

Ranitidine bismuth citrate, a new chemical entity which is a salt complex of ranitidine and bismuth citrate, is being developed for the treatment of relapse of benign gastric and duodenal ulcer and eradication of Helicobacter pylori. The aim of the present study was to establish whether ranitidine bismuth citrate (800 mg) or ranitidine hydrochloride (300 mg) have any effect on gastric emptying of a liquid meal using gamma scintigraphy. On three separate occasions, each of twelve subjects received a single oral tablet of 800 mg ranitidine bismuth citrate, 300 mg ranitidine hydrochloride or placebo in random order. Thirty minutes after dosing each subject was given 375 ml of 99mTc-DTPA (diethylene triaminepentaacetic acid) labelled Clinifeed-ISO. The primary endpoint was the time to 50% gastric emptying (t50%). The proportion of the meal remaining was summarised by weighted mean proportion of the meal remaining in the stomach over 0-60 min and 0-180 min, separately. No differences were observed for t50%, weighted mean 0-60 min, and weighted mean 0-180 min between any two treatments. In man, we have detected no significant effect of single oral doses of ranitidine bismuth citrate 800 mg or ranitidine hydrochloride 300 mg on the rate of gastric emptying of a liquid meal when compared with placebo.

Adult↗
PubMed1994

Development of physical fitness standards for Canadian Armed Forces older personnel.

The purpose of the study was to develop a minimum physical fitness standard for Canadian Forces personnel, 35 years and older, based on common criteria for physically demanding tasks. A random sample of 100 men and 76 women performed the Exercise Prescription (EXPRES) test and five physically demanding tasks that simulate common military tasks, while restricted, for safety reasons, to 90% maximal predicted heart rate. Results indicated poor predictive power, as variances ranged from 5 to 55% between EXPRES fitness scores and task performance. With approval from an expert panel, the 75th percentile score for each task was selected as the cutting criterion. The passing-group data were converted to Z-scores in order to determine the 5th percentile from each EXPRES item: these scores became the EXPRES fitness standard. The minimum fitness standard had a greater impact on women than on men but was representative of the passing groups for both sexes.

Adult↗
PubMed1994

Activity of 4-quinolones against Pseudomonas aeruginosa.

The minimum inhibitory concentrations (MICs), bactericidal activities and mechanisms of action of ofloxacin (CAS 82419-36-1), levofloxacin (CAS 100986-85-4) and ciprofloxacin (CAS 86393-32-0) were investigated against Pseudomonas aeruginosa. All three 4-quinolones were found to possess higher MICs against Pseudomonas aeruginosa than against other Gram-negative bacteria. Despite this, however, all three drugs were more rapidly bactericidal and produced a greater level of kill against Pseudomonas aeruginosa than against any other bacterial species previously tested. Thus MIC tests cannot be used to predict the bactericidal activity of 4-quinolones. Furthermore, MIC tests showed ciprofloxacin to be more potent than ofloxacin or levofloxacin against Pseudomonas aeruginosa. However, bactericidal tests showed levofloxacin to be about 10 times more bactericidal than either ciprofloxacin or ofloxacin. Thus MIC tests cannot predict the relative bactericidal potency of 4-quinolones against Pseudomonas aeruginosa. Therefore, MIC tests should not be used as the sole measure for the efficacy of 4-quinolones, as is often the case. Surprisingly, the characteristic biphasic dose response curve, normally shown by 4-quinolones against other bacteria, was absent when Pseudomonas aeruginosa was tested. This unusual effect was explained by the presence of bactericidal mechanism B associated with the unique loss of bactericidal mechanism A at high 4-quinolone concentrations. This loss of bactericidal mechanism A may explain the recent high incidences of chromosomally-mediated 4-quinolone resistance with Pseudomonas aeruginosa because it may be easier for Pseudomonas aeruginosa to mutate to resist one mechanism of action than to mutate to resist two or more mechanisms of action.

Anti-Infective Agents↗
PubMed1994

Effects of temperature on the bactericidal activities of ciprofloxacin and levofloxacin against Escherichia coli and Pseudomonas aeruginosa.

The bactericidal activities of the 4-quinolones ciprofloxacin and levofloxacin against Escherichia coli and Pseudomonas aeruginosa in nutrient broth were drastically reduced as the temperature of incubation was decreased from 37 to 30 to 25 to 20 degrees C. With E. coli a biphasic response was observed with either 4-quinolone at any one of the four temperatures tested. At the optimum bactericidal concentrations (OBCs) of ciprofloxacin or levofloxacin against E. coli the activity at 20 degrees C was 68- and 56-fold less than at 37 degrees C, respectively. As expected, with P. aeruginosa biphasic responses were not observed so OBC values could not be estimated. At the peak serum concentrations of ciprofloxacin or levofloxacin the bactericidal activity against P. aeruginosa was reduced by 61- or 50-fold, respectively, as temperature was decreased from 37 to 20 degrees C. This was similar in scale to the reductions in bactericidal activity observed with E. coli at its OBC values.

Ciprofloxacin↗
PubMed1994

Effects of temperature on the bactericidal activities of ciprofloxacin and levofloxacin against Staphylococcus aureus and Staphylococcus epidermidis.

The bactericidal activities of the 4-quinolones ciprofloxacin and levofloxacin against Staphylococcus aureus and Staphylococcus epidermidis in nutrient broth were dramatically reduced when the temperature of incubation was decreased from 37 to 20 degrees C. For S. aureus the relative reduction in the activities was 86- and 46-fold with ciprofloxacin or levofloxacin, respectively. For S. epidermidis the corresponding reduction in activities was 82- and 19-fold, respectively. At infectious sites which are at lower-than-body temperature the reduced activity of 4-quinolones may contribute to clinical failure and/or the development of resistance. Levofloxacin was more bactericidal than ciprofloxacin against either of the staphylococci at every temperature tested. These results tend to suggest that levofloxacin may be preferable to ciprofloxacin for staphylococcal infections especially at skin and soft-tissue sites.

Body Temperature↗
PubMed1994

The importance of oxygen in the killing of bacteria by ofloxacin and ciprofloxacin.

There is an inoculum size effect associated with the bactericidal potency of 4-quinolones. This phenomenon has previously been attributed to anaerobic conditions at high initial inoculum sizes. The level of anaerobicity present with Escherichia coli and Staphylococcus aureus at varying initial inoculum size was analysed by measuring dissolved oxygen concentrations and redox potentials. Such measurements confirmed that conditions at high initial inoculum sizes are more anaerobic than conditions at low initial inoculum sizes. The precise concentration of oxygen at which 4-quinolones are no longer able to kill bacteria could not be deduced by either method. The results suggest that extremely low oxygen levels are needed to antagonise 4-quinolone kill. This explains why very stringent conditions are required to render media anaerobic enough to prevent the bactericidal activity of 4-quinolones against bacteria at low initial inoculum sizes.

Ciprofloxacin↗
PubMed1994

Antagonism between bactericidal activities of 4-quinolones and coumarins gives insight into 4-quinolone killing mechanisms.

At concentrations exceeding their MICs, novobiocin and coumermycin antagonised the bactericidal activities of nalidixic acid, ciprofloxacin, ofloxacin and norfloxacin against Escherichia coli KL16. The sensitivities to killing by ciprofloxacin of four mutant derivatives of KL16 carrying gyrA, nalB, nal24 or nal31 alleles were also antagonised by novobiocin. The activities of drug combinations were tested in nutrient broth, which allowed expression of 4-quinolone killing mechanisms A, B and C. They were also tested in nutrient broth plus rifampicin to inhibit mechanisms A and C of the 4-quinolones, and in phosphate-buffered saline, which inhibited mechanism A. Results showed that novobiocin antagonised mechanism C, but not B, of both ciprofloxacin and ofloxacin, but did not antagonise mechanism C of norfloxacin. A review of these and other data indicates that mechanism B may result from the activities of SOS error-prone DNA repair on an irreversibly-bound drug-gyrase-DNA complex, and that mechanism C is mediated via drug interaction with the B subunit of DNA gyrase.

Aminocoumarins↗
PubMed1993

Mechanisms of antimicrobial resistance and implications for epidemiology.

The development of antibacterial agents has provided a means of treating bacterial diseases which were, previously, often fatal in both man and animal and thus represents one of the major advances of the 20th century. However, the efficacy of these agents is increasingly being compromised by the development of bacterial resistance to the drugs currently available for therapeutic use. Bacterial resistance can be combated in two ways. New drugs to which bacteria are susceptible can be developed and policies to contain the development and spread of resistance can be implemented. Both strategies require an understanding of the mechanisms of drug resistance, its epidemiology and the role of environmental factors in promoting resistance. Over the past thirty years our knowledge of bacterial resistance has increased dramatically mainly due to new technology that has become available. Bacteria are able to resist antibacterials by a variety of mechanisms: for example, altering the target to decrease susceptibility to the antibacterial, inactivating or destroying the drug, reducing drug transport into the cell or metabolic bypass. These drug resistance determinants are mediated via one of two distinct genetic mechanisms, a mutation in the bacterial chromosome or by a transmissible element; either a plasmid or a transposon. Significant differences exist between these two types of drug resistance as transmissible resistance, which is mainly plasmid-mediated, permits intraspecies and even interspecies transfer to occur. In contrast, chromosomal resistance can only be passed on to progeny. Transmissible antibacterial resistance is the major cause of concern as it can lead to the rapid spread of antibacterial resistance and has proven difficult, if not impossible, to eradicate. Furthermore, plasmids and transposons can code for multiple antibiotic resistance as well as virulence genes. Antibacterials for which transferable resistance has been identified include most commonly used antibacterials such as beta-lactams, aminoglycosides, macrolides, sulphonamides, tetracyclines, chloramphenicol and trimethoprim. One notable exception is the 4-quinolones for which plasmid-mediated resistance has yet to be identified.

Anti-Bacterial Agents↗